Asunto(s)
Rechazo de Injerto/prevención & control , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Mucorales/aislamiento & purificación , Mucormicosis/diagnóstico , Antifúngicos/administración & dosificación , Mejilla , Desbridamiento , Rechazo de Injerto/inmunología , Humanos , Huésped Inmunocomprometido , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Mucormicosis/inmunología , Mucormicosis/microbiología , Mucormicosis/terapiaAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Receptores de Interleucina-6/antagonistas & inhibidores , Anciano , Biomarcadores , COVID-19 , Infecciones por Coronavirus/diagnóstico por imagen , Femenino , Humanos , Inflamación/tratamiento farmacológico , Trasplante de Riñón , Pandemias , Neumonía Viral/diagnóstico por imagen , SARS-CoV-2 , Receptores de TrasplantesRESUMEN
BACKGROUND: Despite its well-characterized association with poor long-term graft outcomes, subclinical antibody-mediated rejection (ABMR) in recipients of kidney transplants continues to pose a significant diagnostic and therapeutic challenge. Specifically, its detection currently relies on invasive histologic surveillance, a relatively uncommon practice among US transplant centers. We describe a subclinical, "pre-histologic" antibody-mediated rejection identified and characterized by a combination of novel molecular tools, donor-derived cell-free DNA (dd-cfDNA), and molecular histology. CASE REPORT: A 67-year-old kidney transplant recipient was found to have a marked elevation of dd-cfDNA on routine testing at 3 months post-transplant; other laboratory parameters were stable. A biopsy was performed, demonstrating the absence of rejection by traditional histology, but evidence of rejection was seen when tissue was evaluated using a research use molecular histology assay. Four months later, in the setting of persistently elevated dd-cfDNA, the patient developed graft dysfunction and was found to have C4d-negative ABMR, which was treated with improvement in both graft function and dd-cfDNA. CONCLUSION: This case highlighted the complementary use of dd-cfDNA and molecular histology to aid in the early detection and characterization of graft injury. Hybrid approaches combining these tools may allow more expeditious therapeutic intervention, leading to improved graft and patient outcomes.
Asunto(s)
Ácidos Nucleicos Libres de Células , Trasplante de Riñón , Humanos , Anciano , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/genética , Trasplante de Riñón/efectos adversos , Anticuerpos , Expresión Génica , Donantes de TejidosRESUMEN
OBJECTIVES: The number of elderly kidney transplant recipients is increasing, and age-tailored induction immunosuppression regimens are needed. We compared safety and efficacy of basiliximab versus thymoglobulin at various dosages. MATERIALS AND METHODS: Of 590 kidney transplants at our center from 2012 to 2019, 119 (20.1%) were for recipients over 65 years of age; 118 patients received deceased donor kidneys, and 1 received a related living donor kidney. We retrospectively reviewed medical records for demographics, baseline characteristics, donor characteristics, induction regimens, infectious complications, graft function, and patient survival. RESULTS: Patients were subdivided into the following 4 induction immunosuppression groups: basiliximab (n = 15, 12.6%), 3 mg/kg thymoglobulin (n = 8, 6.7%), 4.5 mg/kg thymoglobulin (n = 67, 56.3%), and 6 mg/kg thymoglobulin (n = 29, 24.4%). All patients received pulse doses of methylprednisolone followed by a prednisone taper. Other maintenance immunosuppression agents included tacrolimus and mycophenolic acid. Recipients in the basiliximab and 3 mg/kg thymoglobulin groups were older (median age ⟩70 years; P ⟨ .001). The 4.5 and 6 mg/kg thymoglobulin groups had higher proportions of African American patients and patients with calculated panel reactive antibody over 20%. There were significantly fewer infectious complications in the basiliximab and 3 mg/kg thymoglobulin groups. Despite differences in biopsy-proven acute rejection rates, estimated glomerular filtration rate and graft and patient survival rates at 1 year were similar across groups. All patients with biopsy-proven acute rejection were African American patients. CONCLUSIONS: Kidney transplant in patients ≥65 years is safe and feasible. Changes in this unique population's immune system warrant age-tailored regimens. We found that patients at low immunologic risk would benefit from basiliximab orthymoglobulin at 3 mg/kg. Regardless of calculated panel reactive antibodies, African American patients should be considered as high immunologic risk group forrejection, and higher thymoglobulin dosing should be considered.